The questions addressed in the proposed experiments concern the mechanisms that regulate the survival and ultimate population size of specific groups of neurons in the chick embryo. Although spinal cord limb motoneurons constitute the major cell type to be examined, other populations of spinal cord and brainstem neurons will also be studied. These include: Hofmanns nucleus major; the dorsal magnocellular column (Clarkes column); the column of von Lenhossek; and the nucleus ruber. The major phenomena to be examined in these latter four cell groups are: cell birthdates; naturally-occurring cell death; afferent and efferent cellular interactions, and their role in the survival and differentiation of these various neuronal groups. With regard to spinal cord limb motoneurons, the proposed experiments are aimed at extending past work from our laboratory in which specific mechanisms of neuron-target interactions were examined. In particular, we will focus on interactions in which both synaptic transmission and putative maintenance (i.e. trophic or survival) factors may be involved. Using both in ovo and organ bath preparations we propose to explore the specific contributions of synaptic transmission to neuronal survival. Furthermore, the relationship between synaptic transmission, muscle development and neuronal survival will be examined. Trophic factors isolated from nerve and muscle will be tested in ovo with regard to their effects on both neuronal survival and muscle development. Because it seems plausible that at least certain human neuropathological disorders may involve defects in the normal control of neuronal survival the proposed studies represent an important attempt to better characterize this phenomenon.